In this December 2008 file photo, health workers slaughter all the chickens at the wholesale poultry market in Hong Kong after three dead chickens tested positive for bird flu. The U.S. government asked scientists Dec. 20, 2011, not to reveal all the details of how to make a version of the deadly bird flu that they created in labs in the U.S. and Europe. (Kin Cheung/AP)

By David BrownDecember 20, 2011

Scientists seeking to fight future pandemics have created a variety of “bird flu” potentially so dangerous that a federal advisory panel has for the first time asked two science journals to hold back on publishing details of research.

In the experiments, university-based scientists in the Netherlands and Wisconsin created a version of the so-called H5N1 influenza virus that is highly lethal and easily transmissible between ferrets, the lab animals that most closely mirror human beings in flu research.

Members of the National Science Advisory Board for Biosecurity, which was created after the anthrax bioterrorism attacks of 2001, worried that such a hazardous strain might be intentionally or accidentally released into the world if directions for making it were generally known.

After weeks of reviewing papers describing the research, the NSABB said Tuesday it had recommended that the experiments’ “general conclusions” be published but not “details that could enable replication of the experiments by those who would seek to do harm.”

“Censorship is considered the ultimate sin of original research. However, we also have an imperative to keep certain research out of the hands of individuals who could use it for nefarious purposes,” said Michael T. Osterholm, a member of the board who is also director of the Center for Infectious Disease Research and Policy at the University of Minnesota. “It is not unexpected that these two things would clash in this very special situation.”

The board cannot stop publication. Its advice went to the Department of Health and Human Services, whose leaders asked the authors of the papers and the journals reviewing them — Science, published in Washington, and Nature, published in London — to comply.

The journals’ responses to the request were chilly, although both hinted they were willing to go along under certain conditions. Dutch researchers said they “are currently working on a new manuscript that complies with the recommendation.” The scientists at the University of Wisconsin could not be reached.

The work was paid for by the National Institutes of Health as part of a large portfolio of research aimed at “pandemic preparedness.”

The recommendation from the board puts the federal government in a distinctly controversial and embarrassing position.

It calls for a limit on the free exchange of information — something viewed as anathema by most scientists. It also suggests there wasn’t sufficient forethought about what might happen if the experiments actually worked.

“I hope that in the future we consider the consequences of these experiments long before we get to the publication phase,” said Paul S. Keim, a prominent microbiologist at Northern Arizona who chairs the NSABB.

The board, which has 23 voting members who are academic scientists and public health officials and 18 nonvoting government officials, reached the decision unanimously, Keim said. “The feeling was we need time for a broad, global discussion of the issues in this area,” he said.

The substance of the experiments has been known to some members of the influenza research community since early summer. There are strong and widely divergent views of what should be done with the results. A few scientists say the work should never have started.

About 600 people, mostly in Southeast Asia, have become ill from the H5N1 virus since 1997. About 60 percent have died. The virus is rarely passed from person to person; in most cases, infection requires close contact with sick birds.

Because of its extreme virulence, H5N1 has been the flu strain most feared as the source of a possible influenza pandemic. What it lacked were the genetic changes permitting easy transmission by coughing, sneezing and touch. The new research has apparently produced those changes for the first time — at least in ferrets.

Exactly how the key new mutations occurred is unclear, although it seems in part to be the product of chance. Influenza viruses are constantly changing in small ways, which is one of the reasons vaccines against them have to be reformulated every few years. Simply infecting ferrets enough times with the virus may have been sufficient to allow mutations favoring easy transmissibility to emerge by chance and then be “saved” by natural selection.

In a recent press report in Science, Ron Fouchier of Erasmus Medical Center in Rotterdam said the new strain had five mutations in two genes. All the mutations had previously been seen in flu viruses, but never together.

Bruce Alberts, Science’s editor, said “we strongly support the work of the NSABB” but expressed concern about “withholding potentially important public-health information from responsible influenza researchers.”

The journal’s decision will “be heavily dependent” on whether the government sets out a written plan ensuring that “responsible scientists” who want to read the complete papers to aid their work will be able to. A spokeswoman said this was the first time Science had fielded such a request since it became the journal of the American Association for the Advancement of Science in 1900.

Philip Campbell, the editor of Nature, Science’s chief rival, said he “noted the unprecedented . . . recommendations” and that he was “discussing with interested parties how, within the scenario recommended by NSABB, appropriate access to the scientific methods and data could be enabled.”

One experiment was done at Erasmus Medical Center and the other, led by virologist Yoshihiro Kawaoka, was done at the University of Wisconsin at Madison and the University of Tokyo.

There were two main purposes.

One was to provide researchers with a strain of virus that might be used to make a better vaccine against H5N1 than the one licensed by the Food and Drug Administration several years ago. The second was to give researchers information about what mutations to look for in ongoing surveillance of emerging strains of bird flu — strains that might be inching toward “pandemic potential.”

The newly made strains reportedly have lethality rates in ferrets of 60 to 80 percent and can be passed between animals in adjacent cages. Such a pathogen would make a poor bioterrorism weapon, as it could not be controlled. Nevertheless, many experts believe it could be intentionally or accidentally released — either of which could have devastating consequences.

“These scientists have the best intentions,” said Thomas V. Inglesby, a physician who directs the University of Pittsburgh’s Center for Biosecurity. “That being said, I’m not convinced this work was worth the potential risks.”

Others feel quite differently.

“I think this is really hyped up, and certainly I think not to publish it is ridiculous,” said Peter Palese, a prominent flu virologist at Mount Sinai School of Medicine in New York.

He also said he is not convinced the strains would actually be more hazardous to human beings than the currently circulating ones. “If it is so easy to do in a few mutations, why hasn’t nature done it?” he asked. “These viruses have been around for decades. It has been safely shown that nature has tried this experiment many times.”

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